ANTIVIRAL ACTIVITY OF ALPHA-INTERFERON IN SINDBIS VIRUS-INFECTED CELLS IS RESTORED BY ANTI-E2 MONOCLONAL-ANTIBODY TREATMENT

Pretreatment of AT3 rat prostatic carcinoma cells expressing the inhib itor of apoptosis bcl-2 (AT3-bcl-2 cells) with alpha interferon (IFN-a lpha) affected replication of a virulent strain of Sindbis virus (SV) but did not protect against virus-induced cell death. Treatment of cel ls with IFN-alpha late during infection affected ongoing SV replicatio n very little. Previous studies have shown that cross-linking of the v iral glycoprotein E2 with antibody delays the inhibition of K+ influx by improving the function of Na(+)K(+)ATPase and the Na+-K+-2Cl(-) cot ransport system in SV-infected cells (P. Despres, J. W. Griffin, and D . E. Griffin, J. Virol. 69:7006-7014, 1995). In these studies, we have shown that treatment of infected cells with anti-E2 monoclonal antibo dy also restored the ability of IFN-alpha to induce antiviral activity in infected cells late during infection. The very low rate of virus r elease in SV-infected cells treated simultaneously with anti-E2 monocl onal antibody and IFN-alpha was postulated to be linked to inhibition of virus maturation. Synergistic effects of antibody and IFN-alpha are likely to he important for control of SV replication in vivo.